Drosophila is one of a handful of model organisms used extensively in biomedical research. Importantly 60% of human disease genes are conserved in the fly. Genetic analysis in Drosophila has focused primarily on a whole organism approach but cell lines have also been at the forefront of research because of their utility in biochemical analysis. Moreover, the recent development of cell-based RNAi screens, which have the potential to assay the function of all genes, has further highlighted the importance of cell lines. With these developments has come the realization that the small number of poorly characterized cell lines, with ill-defined cell origins, will limit the full potential of these approaches in Drosophila. Correspondingly, there is a broad consensus in the field that efforts should be made to develop cell-type specific Drosophila cell lines. The goal of this proposal is to address these needs by 1) improving the utility of existing cell lines through genome-wide expression analysis and 2) to develop a genetic method to immortalize/transform Drosophila primary cells. This method will be targeted to specific tissues to derive cell-type specific cell lines. Preliminary results showing that expression of a highly conserved oncogene can induce cell proliferation in primary cells support this goal. The completion of this work is expected to significantly increase understanding of the mechanisms of cell immortalization and transformation in Drosophila and to generate several cell-type specific cell lines. These cell lines will be distributed to the community and the information about them disseminated on a web site. Subsequent use of the cell lines by individual investigators to study diverse biological problems is expected to impact our understanding of human disease.